Studies from our laboratory have provided the basis for considering galanin (GAL) as a neuroendocrine modulator and/or regulator, which participates in the control of gonadal functions. The actions of GAL on the reproductive axis are exerted by endocrine, autocrine and paracrine mechanisms. During the last year, we have provided compelling evidence for most of these mechanisms as well as established a physiological role for the peptide in the control of reproductive events such as the hormonal surges associated with ovulation. Examples for endocrine, autocrine and paracrine regulation by GAL are: the active secretion of the peptide into the hypophyseal portal circulation, the ability of GAL to regulate its own secretion rate from the arcuate nucleus GALergic network, and the actions of GAL secreted from certain pituitary cells for modulating the secretion of others, respectively. Galanin is able to regulate LHRH secretion from arcuate nucleus-median eminence fragments in vitro and requires intact noradrenergic and prostaglandin systems for expressing its effects. Although this constitutes an important observation, the characteristics of the experimental approach do not allow one to distinguish whether the actions of GAL are exhibited directly on the LHRH neuron or are mediated through an interneuronal system. Recently, we have undertaken this question by evaluating the effects of GAL on LHRH secretion from an immortalized LHRH neuronal line. The preliminary results indicate that the peptide has a direct action on RH neurons to enhance their secretory activity. Since GAL is secreted into the portal vasculature, it could act at the level of the gonadotrophs to both stimulate basal secretion and enhance LHRH-induced LH release. However, recent studies have indicated that GAL synthesized within the pituitary contributes to the final gonadotropin output from the pituitary. Using an anti-GAL serum developed in our laboratory, we have been able to show that the blockade of GAL actions in dispersed pituitary cells reduces basal LH secretion. Therefore, GAL is a hypothalamic-hypophysiotropic hormone which regulates, under physiological conditions, LH secretion by acting at the level of the LHRH neuronal system and the pituitary gland as either an endocrine (GAL in portal circulation) or paracrine (intrapituitary GAL) regulator.